NEURAL CONTROL OF LUTEINIZING HORMONE SECRETION IN AGING

衰老过程中黄体生成素分泌的神经控制

• 批准号: 6029801
• 负责人: SANDRA J. LEGAN
• 金额: $ 21.22万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-16 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6029801
• 关键词: aging; alpha antiadrenergic agent; circadian rhythms; estradiol; estrus; female; gonadotropin releasing factor; hormone regulation /control mechanism; hypothalamic pituitary axis; hypothalamus; juvenile animal; laboratory rat; luteinizing hormone; mature animal; microdialysis; neural transmission; neuroregulation; neurotransmitter transport; norepinephrine; ovariectomy; prazosin; radioimmunoassay; secretion

The long-term goal of this proposal is to elucidate the role of changing hypothalamic function in age-related reproductive dysfunction in females. In young rats, norepinephrine (NE) mediates the positive and negative feedback actions of estradiol that govern hypothalamic luteinizing hormone releasing hormone (LHRH), and thereby pituitary luteinizing hormone (LH) secretion. In those middle-aged rats that are still exhibiting regular estrous cycles, the responses to both the positive and negative feedback actions of estradiol are diminished, and circadian rhythms are disrupted, leading to changes in basal LH secretion and LH surges. It remains to be determined whether these age-related changes in LH secretion, that may be harbingers of reproductive dysfunction and senescence, are caused by alterations in NE release in the vicinity of the LHRH neurons. Therefore this proposal will focus on the role of NE in the age-related decrease in the negative and positive feedback actions of estradiol on LH secretion. The FIRST SPECIFIC AIM will test the hypothesis that the basal NE release in the diagonal band of estradiol-treated ovariectomized (OVX+E) rats increases with age and that the early and late increases in release associated with the LH surge in young rats are attenuated or abolished in middle-aged rats. The SECOND SPECIFIC AIM will test the hypothesis that replacement with a pattern of NE release typical of young rats into the diagonal band of middle-aged rats restores the timing and magnitude of the LH surge to those of young rats. The THIRD SPECIFIC AIM will test the hypothesis that the early increase in NE release in the diagonal band of young OVX+E rats is the priming and/or timing signal for the LH surge. The FOURTH SPECIFIC AIM will test the hypothesis that the late increase in NE release in the diagonal band of young OVX+E rats, which occurs at the peak of the LH surge, controls the magnitude of the LH surge. The proposed studies will determine NE release in the region of the LHRH cells bodies in conscious, freely-moving animals by in vivo microdialysis with high pressure liquid chromatography. These studies are critical to our understanding of central nervous system mechanisms that mediate reproductive senescence because they will determine the role of NE in the feedback actions of estradiol on LH secretion and will determine the role of these mechanisms in reproductive aging.

该提议的长期目标是阐明改变的作用 女性与年龄相关的生殖功能障碍的下丘脑功能。 在年轻大鼠中，去甲肾上腺素（NE）介导了阳性和阴性 雌二醇的反馈动作控制下丘脑黄体激素 释放激素（LHRH），从而垂体黄体激素（LH） 分泌。 在那些仍在常规的中年大鼠中 发情循环，对正反馈和负面反馈的响应 雌二醇的作用减少，昼夜节律被干扰， 导致基底LH分泌和LH潮流变化。 还有 确定这些与年龄相关的LH分泌变化是否可能是 生殖功能障碍和衰老的前提是由 LHRH神经元附近NE释放的改变。 所以 该提案将重点介绍NE在与年龄相关的下降中的作用 雌二醇对LH分泌的负反馈作用。 第一个特定目的将检验基础NE释放的假设 在雌二醇治疗的卵巢（OVX+E）大鼠的对角线带中 随着年龄的增长而增加，发行的早期和晚期增加 与年轻大鼠的LH激增相关 中年大鼠。 第二个特定目的将检验以下假设 用典型的年轻大鼠的NE释放模式代替 中年大鼠对角线带恢复了 lh向年轻大鼠的激增。 第三个特定目标将测试 假设NE释放在对角线带的早期释放的早期增加 年轻的OVX+E大鼠是LH激增的启动和/或计时信号。这 第四个特定目标将检验以下假设：NE的晚期增加 在年轻OVX+E大鼠的对角线带中释放，该带发生在峰值 LH激增控制LH激增的幅度。 提议 研究将确定NE释放在LHRH细胞体的区域 在有意识的，自由移动的动物中，通过体内微透析高 压力液相色谱。 这些研究对我们至关重要 了解中枢神经系统机制的介导 生殖衰老，因为它们将确定NE在 雌二醇对LH分泌的反馈动作，并将确定角色 这些机制在生殖衰老中。